Cost-effectiveness of Platelet Function-Guided Strategy with Clopidogrel or Ticagrelor

Some patients treated with dual antiplatelet therapy (DAPT) following acute coronary syndrome (ACS) can still exhibit heightened residual platelet reactivity (HRPR), which is potentially linked to adverse vascular outcomes. Better tailored DAPT strategies are needed to address this medical need. Aim: To assess the cost-effectiveness of guided DAPT with clopidogrel or ticagrelor in addition to aspirin when using VerifyNow P2Y12 testing in post-ACS patients. Methods: The costs were calculated per 1,000 patients aged >55 years. It was assumed that all patients received either generic clopidogrel or ticagrelor for 1 year, and underwent VerifyNow P2Y12 assay testing before DAPT maintenance. Results: Guided DAPT will prevent five more MIs and six more deaths per 1,000 patients than a standard prescription of generic clopidogrel. The total predictive value of costs per patient is 32% lower if a guided strategy is used than if ticagrelor is given to all patients. Conclusion: Assessment of heightened residual platelet reactivity with P2Y12 assay in triaging DAPT post-ACS patients for 1 year is a cost-effective strategy that would reduce financial burden compared to routine administration of more expensive antiplatelet agents

Solid cancers after antiplatelet therapy: Confirmations, controversies, and challenges

© Schattauer 2015. The role of anticoagulants and antiplatelet agents in tumour growth and prognosis is not new, and currently under intense investigation. Some randomised data strongly suggest that this association exists, but it is complex, and not necessarily pointed at the same direction. The potential mechanisms responsible for such harmful association include a direct hazard of novel antithrombotics on cancer, indirect promotion of tumour growth, easier metastatic dissemination due to instability of platelet-tumour cell aggregates, or/and inability to keep cancer cells locally in situ are considered. The latest randomised evidence ultimately rejected the drug-specific cancer risks, clearly indicating the class-effect. In lay terms “cancers follow bleeding”, which seems to be true for antithrombotic agents in general. Significant excess of solid cancers which was similar after prasugrel in TRITON, and with vorapaxar in TRACER trials was confirmed by the FDA reviews. Later, extra cancer deaths reported following clopidogrel and prasugrel in DAPT, and after ticagrelor in PEGASUS are also of concern. However, there are remaining controversies with regard to published cancer risks after ticagrelor (PLATO), or another vorapaxar trial (TRA2P), while full disclosure of separate clopidogrel and prasugrel cancer data in DAPT is still lacking. In short, if we apply moderate antiplatelet strategies for over two years, or aggressive regimens including triple therapy for much less than one year, the solid cancer risks emerge. Currently, more delicate platelet inhibition, and shorter exposure to dual oral antiplatelet agents should prevail

The CYP2C19*1/*2 Genotype Does Not Adequately Predict Clopidogrel Response in Healthy Malaysian Volunteers

Background. The CYP2C19*2 allele may be associated with a reduced antiplatelet effect for clopidogrel. Here, we assessed whether CYP2C19*2 alleles correlate with clopidogrel responsiveness following the administration of clopidogrel in healthy Malaysian volunteers. Methods. Ninety volunteers were genotyped for CYP2C19*2 and CYP2C19*3 alleles. Forty-five of 90 volunteers were included in the clopidogrel response studies and triaged into three genotypes, namely, CYP2C19*1/*1 (n=17), CYP2C19*1/*2 (n=21), and CYP2C19*2/*2 (n=7). All subjects received 300 mg of clopidogrel, and platelet reactivity was assessed after a four-hour loading utilizing the VerifyNow-P2Y12 assay. Platelet activity was reported using P2Y12 reaction units (PRUs), and nonresponder status was prespecified at PRU ≥ 230. Results. Following clopidogrel intake, CYP2C19*2/*2 carriers had a significantly higher mean PRU compared to the CYP2C19*1/*2 and CYP2C19*1/*1 (291.0 ± 62.1 versus 232.5 ± 81.4 versus 147.4 ± 87.2 PRU, P<0.001) carriers. Almost half of the participants (46.7%) were found to be nonresponders (3 were CYP2C19*1/*1, 11 were CYP2C19*1/*2, and 7 were CYP2C19*2/*2). Conclusion. In healthy Malaysian volunteers, CYP2C19*2 allele was associated with a decrease in platelet responsiveness to clopidogrel. However, clopidogrel nonresponders can be found not only in the carriers of CYP2C19*2/*2, but also in the carriers of CYP2C19*1/*2 and CYP2C19*1/*1. The present paper demonstrated that genotype information does not correlate with clopidogrel response, and genotyping may represent a less robust approach compared to platelet activity testing in guiding clopidogrel therapy

Underutilization of gastroprotection for at-risk patients undergoing percutaneous coronary intervention: Spain compared with the United States

Aliment Pharmacol Ther 2010; 32: 689–695Proton pump inhibitors (PPIs) are the preferred agents for the prevention of aspirin-associated upper gastrointestinal bleeding (UGIB). Data are limited to determine whether PPIs are being used to reduce UGIB risk.To evaluate the implementation of PPI treatment to reduce the GI risk in two cardiology centres from Europe and the United States.A retrospective cross-sectional study was carried out at the University of Michigan and University Hospital-Zaragoza in 429 consecutive patients hospitalized for percutaneous coronary intervention (PCI) on dual antiplatelet therapy.Admission for PPI co-therapy was similar (34% vs. 30%) in both centres. At discharge, the proportion of high-risk patients receiving PPI therapy in the Spanish centre (75.4%) was higher than their American peers (55.6%) (OR: 2.5; 95% CI; 1.3–4.7). No differences in PPI prescription rates were found among Spanish patients with/without GI risk factors. The opportunity to initiate PPI co-therapy in high-risk patients was missed in 81.8% (36/44) of those not on PPI at admission in US patients vs. 24.1% (19/79) ( P  <   0.0001) in Spanish patients.There are important differences concerning PPI prescription and risk stratification in the two centres when managing PCI patients. Efforts to stratify risks and utilize appropriate strategies for UGIB prophylaxis in high-risk patients are warranted.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79078/1/j.1365-2036.2010.04393.x.pd

Clinical Considerations with the Use of Antiplatelet Therapy in Patients Undergoing Percutaneous Coronary Intervention

Despite the proven benefits of using antiplatelet therapy in patients undergoing percutaneous coronary intervention (PCI), a number of key questions remain to be answered. In recent years, clopidogrel dosing strategies among such patients have evolved considerably, with newer approaches involving loading doses prior to PCI and increases in the time interval and loading dosage in an effort to overcome variable responsiveness/hyporesponsiveness to platelet inhibition. Further, the role of glycoprotein (GP) IIb/IIIa antagonists in elective stenting continues to be defined, with recent evidence suggesting that most appropriate use of these agents is in high-risk patients with elevated troponin levels. There appears to be a relationship between the use of GP IIb/IIIa antagonists with clopidogrel loading and attenuation of early inflammatory and cardiac marker release. Strategies to minimize the chance of late stent thrombosis in patients who receive drug-eluting stents (DES) are also under intense investigation. Among some patients receiving sirolimus and paclitaxel DES, current standard long-term antiplatelet strategies may be insufficient. Patient nonadherence to treatment and premature discontinuation and underutilization of antiplatelet therapies by physicians remain important clinical problems with potentially dire consequences. Copyright © 2008 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58553/1/20359_ftp.pd